Contraception

Hypothalamic pituitary feedback system

Hypothalamus releases GnRH -->

Stimulates anterior pituitary to release LH and FSH -->

Stimulates oestrogen (E) and progesterone (P) release

What is GnRH?

Gonadotropin releasing hormone

Stimulates release of LH and FSH

What is LH?

Stimulates the release of the egg (ovulation) and progesterone

When oestrogen peaks, LH surges to trigger ovulation

What is FSH?

Stimulates growth and maturation of ovarian follicle and oestrogen

Role of oestrogen

When oestrogen peaks, LH surges triggering ovulation

Thickens uterine lining (endometrium)

Role of progesterone

Thickens cervical mucus

Menstrual cycle: phases

Menstrual (day 1-5)

Follicular (day 1-14)

Ovulation (day 14)

Luteal (day 15-28)

Menstrual phase

Marks the beginning of the cycle

Shedding of endometrium through vaginal bleeding

Bleeding lasts for 3-7 days

Oestrogen and progesterone levels are LOW

Follicular phase

Begins on first day of menstruation and lasts until ovulation

Development and maturation of ovarian follicle

FSH is released and oestrogen slowly increases

Progesterone remains LOW

Ovulation phase

Release of mature egg from ovary

Occurs around midpoint of cycle

Triggered by surge of LH due to increased oestrogen levels

Oestrogen is HIGH

Luteal phase

Begins after ovulation and lasts until the start of the next menstrual period

Ruptured follicle transforms into corpus luteum which produces progesterone

Progesterone prepares endometrium for potential implantation

If implantation does not occur, corpus luteum breaks down

Progesterone and oestrogen levels RISE

What are current contraception options?

Fertility awareness methods

Withdrawal method

Male and female

- barrier method

- permanent method

Hormonal method

- combined methods

- progesterone only

Intrauterine methods

Emergency contraception

Hormonal contraceptive options

Contraceptive pills

- COCP

- POP

Vaginal rings

Depot injections

Long acting reversible contraceptives

- implants

- IUDs

Which contraception is the most effective?

Implant

IUD

Male sterilisation

Contraceptive failure rates

70% of women of reproductive age use contraceptive method

>50% women have had an unplanned pregnancy

History of contraceptive pill

70s

- progesterone only pill was introduced

- concerns about COCP and thromboembolic events

80s

- biphasic and triphasic pills introduced

- high-dose oestrogen pills reduced

90s

- low dose pills introduced

2000s

- new progestins introduced

- non-oral combined hormonal contraceptives introduced

2010s

- use of natural estrogens introduced

What is the most common form of contraceptive pill?

COCP

COCP: administration

Taken daily for 21 or 28 days depending on formulation

Withdrawal bleed will normally occur during pill free/placebo days of the 28 days

COCP: first line

Any formulation with

- 30-35 mcg ethinyloestradiol OR 50 mcg mestranol

- levonorgestrel or norethisterone

COCP: multiphasic

Triphasic

- varying E/P across 21 days

- 7 inactive pills

New multiphasic (Qlaira)

- varying E/P across 26 days

- 2 inactive pills

COCP: components

Progestogen

Estrogen

What are progestogens?

Synthetic forms of progesterone

Progestogens suppresses...

Mid-cycle peaks of LH and FSH = blocks ovulation

Endometrial proliferation

Progestogens produce...

secretory endometrium

- prevents cancer of endometrium

Which component of the COCP slows the movement of the ovum?

Progestogen slows movement of ovum

Does progestogen and oestrogen potentiate the action of each other?

Yes

Progestogen does what to the cervical mucus?

Thickens cervical mucus which makes it impermeable to the sperm

What effect does progestogen have on the sperm?

Decreases sperm motility

What effect does progestogen have on cilliary activity?

Reduces cilliary activity on fallopian tubes

Which hormone suppresses FSH?

Both progestogen and oestrogen

Oestrogen _______ development of dominant follicle in follicular progression

prevents

___________ stimulates endometrial proliferation

Oestrogen

Oestrogen: metabolic and side effects

Side effects

- nausea, vomiting

- breast tenderness

- fluid retention

- change in libido

Metabolic effects

- increased HDL, VLDL, TGs

- decreased LDL and bone resorption

- increased coagulation factors (dose-related)

Oestrogen: examples

Ethinyloestradiol

Mestranol

Estradiol

Oestrogen: ethinyloestradiol

Most common due to high oral bioavailability

Oestrogen: estradiol

Rapid inactivation by liver or short half life

Combined with synthetic ester (estradiol valerate) improved bioavailability + half-life

May have more favourable impact on lipid + carbohydrate metabolism

Which formulation of oestrogen has a favourable impact on lipid + carb metabolism?

Estradiol

Which formulation of oestrogen is combined with an ester to improve bioavailability and half-life?

Estradiol --> estradiol valerate

Oestrogen: contraindications

Thromboembolic disorder

Uterine bleeding

Liver disease

Cerebrovascular artery

Coronary artery disease

Breast cancer

Progestogen: side and metabolic effects

Side effects

- menstrual irregularity

- nausea, bloating

- weight gain

- breast tenderness

- changes in libido

- acne, mood changes

Metabolic effects

- decreased HDL, LDL

- increased VLDL

Progestogen: contraindications

Vaginal bleeding

Arteriopathy

Which progestogen is structurally related to testosterone?

Estranes

- norethindrone

Gonanes

- levonergestrel

Which progestogen is structurally related to progesterone?

Pregnane derivatives

- medroxyprogesterone acetate

- cyproterone acetate

19-norpregnane derivatives

- nomegestrol acetate

Which progestogen is structurally related to sprinolactone?

Drosperinone

COCP: main action

Inhibits ovulation

COCP: role of oestrogen

Suppresses the development of ovarian follicles by FSH suppression

Stabilises endometrium to reduce unwanted breakthrough bleeding + irregular shedding

Potentiates action of progestogen by increasing concentration of intracellular progestational receptors

COCP: role of progestogen

Inhibits LH surge which is necessary for ovulation

Produces a non-receptive endometrium

Thick mucus impervious to sperm

COCP: other actions

Hostile cervical mucus and atrophic endometrium --> sperm transport and implantation may be impaired

Monophasic COCP contain how much oestrogen and progestogen?

The same amount throughout each of the 21 active tablets - fixed dose

COCP: examples

See image

Can you change the time of menstruation with monophasic COCP? Why do some women do this?

Yes by carrying on with the next pack of active tablets

You don't take the 7 inactive pills

Some women prefer to have withdrawal bleed only once every three months

- tricycling or extended cycling

What happens if you shorten the hormone free interval?

May reduce incidence of hormone withdrawal symptoms

May increase contraceptive effectiveness

Monophasic COCP options

Zoely (nomegestrol with estradiol)

- 24 active, 4 inactive

- common to have no withdrawal bleed

Yaz (drosperinone with ethinylestradiol)

- 24 active, 4 inactive

- shorter pill free break --> increases contraceptive effectiveness

Seasonique (levonorgestrel with ethinylestradiol)

- extended regimen, taken continuously for 91 days

- no pill free break

- 84 tabs of 150 mcg levonorgestrel + 30 mcg ethinylestradiol

- 7 tabs 10 mcg ethinylestradiol

Nextstellis (drosperinone with esterol)

- esterol (E4) is synthetic analogue of oestrogen

- better effects on CV risk - need more evidence

What is E4?

Estetrol is a synthetic analogue of human oestrogen

It has high selectivity for oestrogen receptors

Binds to both alpha and beta receptors

Which monophasic COCP has no pill free break?

Seasonique

It just has a lower dose of ethinylestradiol during the 7 days

Multiphasic COCP mimics...

normal hormonal cycle

What happens to oestrogen and progestogen in multiphasic COCPs

Oestrogen increased mid cycle to reduce risk of breakthrough bleeding

Progestogen increased incrementally throughout cycle

Why are multiphasic COCPs used sometimes? What are the drawbacks?

Because it provides better cycle control

But,

More complex and more difficult to change the timing of the withdrawal bleed

Multiphasic COCP: side and metabolic effects

Side effects

- cyclical symptoms

- fluid retention

- PMS

Metabolic effects

- low metabolic effects

- less effect on carbohydrates and lipids

Is there any evidence for choosing multiphasic over monophasic?

No

Multiphasic COCP (Qlaira)

Very complicated for user

Combined contraceptive (vaginal ring)

Nuvaring (etonogestrel with ethinylestradiol)

- 3 weekly use + 1 week free

- better adherence + convenient

- localised concentration + steady drug release

- avoid first pass effect + GI absorption

- less ADRs

- same DDIs

Even though the NuvaRing is used locally, it is ____________ absorbed

systemically

COCP: adverse effects

Varies according to

- dose

- combination

- patient

Commonly reported

- breakthrough bleeding (transient)

- nausea/vomiting

- mood changes

- thrust

Rare

- lipid profile changes

- hypertension

- VTE

- stroke

COCP: VTE (risk and CI)

All COCP increase risk of VTE but absolute risk is still low

Risk of VTE depends on

- dose of oestrogen/progestogen

- other risk factors

CI

- family history of VTE

- obese

- prolonged immobilisation

- <21 days post-partum

Progestogens + VTE

The higher the progestogen the higher the risk of VTE

Post-partum is riskiest time for VTE

Medical eligibility criteria for hormonal contraceptives

UKMEC

1 or 2

- safe to use

3

- require expert clinical judgement or referral

4

- absolute contraindications

COCP: UKMEC 3

BMI >35 kg/m2

Diabetes with

- nephropathy

- retinopathy

- neuropathy

History of

- migraine with aura (but not within last 5 years)

- VTE in family

CVD risk factors

Between

- 0-3 weeks postpartum

- 3-6 weeks postpartum

* COCP CI until 6 weeks

COCP: UKMEC 4

Current breast cancer

History of

- migraine with aura (within last 5 years)

- heart disease, stroke

- smoking

- high BP

- VTE

First

- 6 weeks postpartum

- 3 weeks postpartum

Choice of COCP

Lowest dose pill should be used wherever possible

- available as low, standard and high dose

- generally start with low or standard dose

- high dose used with anti-epileptics

Tricycling with monophasic pills useful for patients with menstruation problems

What dose of COCP should patients start on?

Low dose

A high dose of COCP should be used when patients are on what medication?

Anti-epileptics

Tricycling with monophasic pills are useful for patients with?

Menstruation related problems

COCP: managing side effects

Main action is to reduce oestrogen dose for

- headache

- nausea

- breast tenderness

- bloating/fluid retention

If a patient has breakthrough bleeding, they need to increase _________ dose or change __________ dose

oestrogen, progestogen

COCP: counselling

Starting, changing, stopping

After childbirth

Missed pill

Breakthrough bleeding

Skipping a period

If new to OC they start in the...

active tablets on day 1-2 of their menstrual cycle

- first day of bleeding

- no additional contraception required

If new to OC and they're not on their period, they can start...

with active tablets any other time BUT they will not have contraceptive cover until AFTER 7 days

When should the woman get her period while taking COCP?

The period should start 2-3 days after the last 'active' pill is taken

If patient is switching COC when do they start taking the active pills? Do they need additional contraceptive cover?

Start taking active pills the day after you stop your old pill (on any day of your cycle)

Additional contraception is not required

If switching from POP when do they start taking active pills? Do they need additional contraceptive cover?

Start taking active pills without any interval

Use additional contraceptive methods until you have taken active pills for 7 days

If you vomit <2 h of taking an active pill, you should?

Take another active pill ASAP

If you miss a pill <24 h of due time, you should?

Take the missed pill ASAP

PLUS

Take the next active pill when it is due

No additional measures necessary

If you miss a pill and its >24 h late, you should?

Take one active pill when you remember

PLUS

Take the next active pill when it is due

PLUS

Use additional contraception (e.g. condoms) for 7 days of active pills

Which pills are the most dangerous to miss?

Those pills at the beginning or end of the active pill cycle

If the 7 day additional cover extends into the inactive pill week, you should?

Skip the inactive tablets and start the new pack right away

So you will have no withdrawal bleed (period)

If the missed pills occurs 7 days after the inactive pill week, you should?

Seek emergency contraception

Up to how many missed pills can you take?

Only two

NuvaRing: contains? for how long?

Contains:

- 0.015 mg ethinylestradiol

- 0.12 mg etonogestrel

- per day, vaginally

Remains within the vagina for

- 3 of 4 weeks

Nuvaring: if not taking any other form of OCP you should?

Insert the ring vaginally during the first 5 days of the cycle

Nuvaring: if changing from COCP, you should?

Insert the ring immediately or at least within 7 days of the last active pill

Nuvaring: if changing from POP, you should?

Insert the ring the same day as the last active pill is taken

Nuvaring: if ring is expelled within 3 weeks, you should? What about protection?

Re-insert the ring

<3 hours

- protected

<3 hours

- may not be protected

- need additional contraceptive cover till the ring is in place for 7 days

Nuvaring: if the ring is left in for too long, you should?

= 4 weeks

- insert new ring after 1 week free

>4 weeks

- protection is lost

- check pregnancy status

- insert new ring ASAP

- additional contraceptive cover till ring is in place for 7 days

Nuvaring: if the ring breaks, you should?

Remove and discard it

Insert a new ring ASAP

Nuvaring: if the interval >1 week

Check for pregnancy

Insert new ring ASAP

Use additional contraceptive cover till the ring is in place for 7 days

Examples of progestogen only formulations

Levonorgestrel

- oral

- IUD

Norethisterone

Drosperinone

Medroxyprogesterone acetate

- IM

POP: main points

Mini pill

Less effective than COCP

Taken continuously (no inactive pills)

- regular withdrawal bleed may not occur

Useful if oestrogen to be avoided

Less progesterone than COC

Effective within 48 h

e.g.

- levonorgestrel

- norethisterone

POP is useful if __________ is to be avoided

oestrogen

POP protects against pregnancy by...

- thickens cervical mucus thus hindering sperm motility

- making endometrium inhospitable ot fertilised eggs

- slow ovum transport through fallopian tubes

- suppressing ovulation